2. Academic Validation
  3. AdipoRon exerts an antidepressant effect by inhibiting NLRP3 inflammasome activation in microglia via promoting mitophagy

AdipoRon exerts an antidepressant effect by inhibiting NLRP3 inflammasome activation in microglia via promoting mitophagy

  • Int Immunopharmacol. 2024 Nov 15:141:113011. doi: 10.1016/j.intimp.2024.113011.
Yaqi Liu 1,  Xiying Fu 2,  Jiangjin Sun 1,  Ranji Cui 3,  Wei Yang 4
Affiliations

Affiliations

  • 1 Department of Neurology, The Second Hospital of Jilin University, Changchun, Jilin Province, China; Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, Jilin Province, China.
  • 2 Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, Jilin Province, China; Department of Endocrinology, The Second Hospital of Jilin University, Changchun, Jilin Province, China.
  • 3 Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, Jilin Province, China. Electronic address: cuiranji@jlu.edu.cn.
  • 4 Department of Neurology, The Second Hospital of Jilin University, Changchun, Jilin Province, China; Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, Jilin Province, China. Electronic address: wyang2002@jlu.edu.cn.
PMID: 39213872 DOI: 10.1016/j.intimp.2024.113011
Abstract

Depression is a serious mental disorder that threatens patients' physical and mental health worldwide. The activation of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome is essential for microglia-mediated neuroinflammation and neuronal damage in depression. Numerous pathophysiological factors, such as mitochondrial dysfunction and impaired Mitophagy, have an essential role in activating the NLRP3 inflammasome. AdipoRon is a potent Adiponectin Receptor agonist; however, its antidepressant effects have not been thoroughly investigated. In this study, we found that AdipoRon ameliorated depression-like behavior and neuronal damage induced by chronic unpredictable mild stress (CUMS). Further research demonstrated that AdipoRon inhibited the activation of the NLRP3 inflammasome and protected hippocampal neurons from microglial cytotoxicity by promoting Mitophagy, increasing the clearance of damaged mitochondria, and reducing mtROS accumulation. Importantly, inhibition of Mitophagy attenuated the antidepressant and neuroprotective effects of AdipoRon. Overall, these findings indicate that AdipoRon alleviates depression by inhibiting NLRP3 inflammasome activation in microglia via improving Mitophagy.

Keywords

AdipoRon; Depression; Microglia; Mitophagy; NLRP3 inflammasome; Neuroinflammation.

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